Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. The Precision Medicine Initiative (PMI) was recently launched by the NIH to accelerate the pace of discovery. Though initially focused on cancer, the PMI will eventually generate knowledge applicable to a range of diseases, including infectious diseases. Substantial federal and private research funding has been, and will continue to be, devoted to scientific research at the intersection of genomics and infectious disease. In parallel, considerable attention needs to be paid to the possible ethical, legal, social implications (ELSI)-for individuals, groups or the larger society-of using genomic information in the management of infectious disease. Our P20 Exploratory Planning grant was the first to consider these ELSI questions. Drawing on our P20, the proposed CEER, entitled ELSI Issues in Applying `Precision Medicine' to Infectious Disease (#GUIDE2P5), aims to apply a systems perspective to examine the ethical, legal, social, historical and policy issues confronting the incorporation of genomics in the prevention, outbreak control, and treatment of a range of infectious diseases. Our transdisciplinary research plan is organized around three discrete but related program areas, each of which includes 1 pilot project. Each pilot project will highlight a particular type of infectious disease, and use a mixed-methods approach to (1) engage a range of stakeholders in identifying and responding to the ELSI and policy issues; (2) analyze the ELSI issues identified, and (3) develop policy recommendations regarding the integration of genomic information in infectious disease management. In Program Area 1 (Implications for Research), the pilot project will address the impact of research on genetic variation in HIV and HCV transmission in cohorts of at-risk urban populations. In Program Area 2, (Implications for Public Health Policy), the pilot project will analyze the role and impact of advances in vaccinomics for informing population-based prevention. In Program Area 3 (Implications for Clinical Practice), the pilot project will assess the application of genomics in the clinical management of acute, high consequence infectious diseases like MRSA and Ebola. We also propose a robust career development plan that builds on educational programs available in different Divisions of Johns Hopkins. Included are undergraduate public health and bioethics programs, School of Public Health programs including a new master's program in bioethics in partnership with the Berman Institute of Bioethics, Masters in genetic counseling, MPH/JD program, doctoral program in genetic epidemiology, and preventive medicine residency; and School of Medicine programs for medical students and post-doctoral fellows in the history of medicine. Our research and education plans are designed to inform and influence the future research agenda-even as the science is still developing-so that the benefits of genomic applications to infectious disease are maximized while potential harms to individuals and populations are minimized.